GPX4 is a key ferroptosis regulator orchestrating T cells and CAR-T-cells sensitivity to ferroptosis.

ABSTRACT: Induction of ferroptosis, an iron-dependent form of regulated cell death, holds promise as a strategy to overcome tumor resistance to conventional therapies and enhance immunotherapy responses. However, while the susceptibility of tumor cells to ferroptosis is extensively studied, limited data exists on the vulnerability of immune cells to disturbed iron balance and lipid peroxidation. Here, we found that T-cell stimulation rewires iron and redox homeostasis and by increasing levels of reactive oxygen species and labile iron promotes lipid peroxidation and T-cells' ferroptosis. Upon stimulation, we detected changes in the balance of ferroptosis-suppressive proteins, including decrease of GPX4. Subsequently, we identified GPX4 as a master regulator orchestrating T/CAR-T-cells' sensitivity t

SUBMITTER: Klopotowska M 

PROVIDER: S-EPMC12321709 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature